Advances in targeting RNA modifications for anticancer therapy

靶向RNA修饰抗癌治疗的进展

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Abstract

Numerous strategies are employed by cancer cells to control gene expression and facilitate tumorigenesis. In the study of epitranscriptomics, a diverse set of modifications to RNA represent a new player of gene regulation in disease and in development. N(6)-methyladenosine (m(6)A) is the most common modification on mammalian messenger RNA and tends to be aberrantly placed in cancer. Recognized by a series of reader proteins that dictate the fate of the RNA, m(6)A-modified RNA could promote tumorigenesis by driving protumor gene expression signatures and altering the immunologic response to tumors. Preclinical evidence suggests m(6)A writer, reader, and eraser proteins are attractive therapeutic targets. First-in-human studies are currently testing small molecule inhibition against the methyltransferase-like 3 (METTL3)/methyltransferase-like 14 (METTL14) methyltransferase complex. Additional modifications to RNA are adopted by cancers to drive tumor development and are under investigation.

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